Differentiated Thyroid Cancer: 2014 Update

I just attended the 2014 ATA meeting at San Diego. The following are the simplified global themes discussed at the meeting concerning thyroid cancer evaluation.

The theme is to create personalized care based on risk stratification. There is a trend for de-escalation of treatment for low risk patients with less surgery, lower iodine doses and less intense TSH suppression, and to provide tailored cancer specific therapies for high risk patients and those who are symptomatic from the tumor burden. There is also the hope that better prognostication and future therapies will be fine tuned based on the molecular marker profile of the individual patients cancer. These changes are based on the quality of the evidence of the literature at this time. I will discuss type of surgery, whether or not radioactive iodine is given, the degree of TSH suppression with thyroid hormone recommended based on risk stratification. I must say it is an exciting time to be a thyroidologist!

Type of initial treatment depend on the patient and the tumor characteristics. However I cannot emphasize enough that the best treatment for thyroid cancer is a thoughtful and thorough initial surgery by an experienced surgeon who is familiar with risks involved depending on the presentation. This sets the stage for what happens next.

What type of initial treatment?
If a small thyroid cancer is found, we have a choice To observe a small tumor or to operate. The option to observe is particularly a good choice for older patients harboring tiny tumors. These tend to be stable over years.
For small cancers confined to one side of the thyroid we have the options to remove a small tumor with lobectomy or isthmectomy or total thyroidectomy.
For people with bigger tumors or nodules in both sides a total thyroidectomy is best choice
For those with lymph nodes at presentation the thyroidectomy central compartment dissection plus minus Latter lymph node dissection.
For patients whose tumors invade neck structures such as the airway esophagus, neck muscles more aggresive surgeries are indicated.

Who gets radioactive iodine I131 ablation ( to destroy all remnant thyroid tissue after thyroid surgery). We want to avoid giving this therapy in patients who would not benefit from this treatment (because they have a very low risk of dying from the disease) and avoid unnecessary side effects. We want to give it to high risk patients because radioactive iodine has been shown to decrease risk of recurrence and mortality in high risk (stage 3-4) patients. The ATA has defined recurrence risk initially based on operative findings at initial surgery with review of the pathology.

So who Do we ablate with I 131 after surgery?
Low risk patients- no
Microcarcinoma – no
Multifocal microcarcinoma (Excluding those with high risk features, histology etc.) – No
Intermediate risk patients ( this is a spectrum see new ATA guidelines> 4-5 lymphnodes metastasis, and or other high risk features such as older patient, larger tumor, more aggressive histology, molecular markers with Braf v600 and TERT mutations) – Yes
High risk patients ( large lesions, bulky disease, many metastatic lymph nodes, residual macrometastasis, metastatic disease, aggressive histology- Yes

Post operatively thyroglobulin levels ( a marker of residual thyroid tissue or thryoid cancer) should be used also regarding decision on I131. Levels that are low suggest an excellent surgery, higher levels suggest incomplete surgery or a complete surgery but residual thyroid cancer not detected in the neck at the time of the surgery.

Radioactive iodine ablation.
For I131 ablation It is recommended patients have iodine deficient diet for 2 weeks prior to I131 ablation to allow the radioactive iodine to reach the thyroid tissue without having to compete with other body iodine. The success of iodine depletion can be documented by obtaining a 24 hour urine collection and showing iodine of 50 or less for an effective assessment. This is particularly useful if residual disease is suspected but the I131 uptake is negligible.

Recombinant TSH (thyrogen) is equivalent to thyroid hormone withdrawal in effectiveness of thyroid ablation. This has been shown internationally by various investigators.

Some prominent endocrinologists as Dr. Len Wartosky recommend diagnostic scans prior to ablation to guide decision whether or not treat and how much I 131 iodine to give. For the diagnostic scan we utilize I123 or tiny dose of 1-3 mCu I 131 to avoid “stunning” of the gland prior to actual ablation or treatment. However, most endocrinologist proceed directly to ablation with fixed doses of radioactive iodine, unless there is high burden of disease a priori, the patients is very young or old in which cases dosimetry should be done.

How much iodine to give for thyroid remnant ablation after surgery?
It turns out that a small dose of 30 mCi (miillicuries) is as effective as 100 mCi dose and is supported by many studies, so current recommendation is to give 30 mCi for ablation, which is also accompanied by less side effects.

Adjuvant therapy with I131 is used when the surgeon believes that there is residual microscopic and macroscopic disease left, so in this situation we are both treating and ablating remnant thyroid-related tissue. In this scenario a dose 75-150 mCI is recommended.

Reassessment with thyrogen ( recombinant TSH) and a I 131 uptake is recommneded 8-12 months after ablation to assess success of the ablation, measure thyroglobulin and clinically re-stage patients. If there is not I 131 uptake, with an iodine deficient diet preparation, and thyroglobulin is undetectable then the risk of recurrence is extremely low ~2 percent and this documents low risk and therefore less intensive treatment. If there is uptake on the neck, and / or elsewhere further evaluation and treatment is indicated. Pulmonary metastasis often require multiple I131 treatments if they are iodine avid.

TSH suppression has been shown to decrease risk of recurrence and mortality.
The risk of tsh suppression is primarily bone loss in postmenopausal women and the elderly and risk of atrial fibrillation arrythmia after age of 65. Based on all the data I’ve seen I recommend a TSH of < 0.1 in the first 4 years after thyroidectomy and treatment of thyroid cancer. For those assessed to have low risk TSH can be 0.5-2.0 mIU/L after this period, for intermediate risk and high risk a TSH < 0.1 mIU/L is adequate. It appears that < 0.1 is equivalent < 0.02 mIU/l. For patients who are older and have aggressive thyroid cancer for whom TSH suppression is essential, beta blockade is useful as well as therapy to prevent further bone loss if they have osteoporosis or high fracture risk base on FRAX analysis.

For intermediate-moderate to high risk patients with or without symptoms I strongly recommend they be cared for by a multidisciplinary team at a cancer center with expertise and ongoing research and participation in thyroid cancer trials. ( see my website under links for thyroid cancer trials and thyCa links)

Local therapies are recommended for localized disease metastasis, especially if vital structures (airway, vessels, brain, impending fracture) are at risk. Such as radiation or thermal or cryoablation. For patients with bone metastasis either iv bisphosphonate such as reclast or rankle antagonist denosomab is recommended.

For patients whose cancers do not take radioactive iodine (radioiodine resistant disease, but are stable, observation is recommended since systemic therapies such as tyrosine kinase, vgef, MEK, ALT inhibitors have significant side effects that alter significantly quality of life and at this point do not seem to alter mortality. For those who are progressing at measurable rates with RECISt criteria, and are symptomatic it is recommended that that they do get systemic therapies, since these therapies can alter the progression of disease and in some cases make thyroid cancer cancers that are radio-resistant radioactive iodine avid by allowing re-differentiation and expression of the sodium iodine symporter and thereby alter outcome. What is clear is that more that one therapy may be needed to treat aggressive I131 radio-resistant disease.
I have been particularly impressed with trials and data presented by Memorial Sloan Kettering ( DR. Michael Tuttle’s team, MD Anderson clinic (DR. Steve Sherman), Mayo clinic, Ohio state (Manisha Shah), and molecular profiling and prognostication And treatment at the University of Pittsburgh (Dr. Carin). Other centers of excellence appear to be Duke (Dr Sosa and Dr. Roman, Johns Hopkins (Dr. Ziegler and Dr. Doug Ball). On the east coast where I am located I tend to refer for surgery and work closely with the multi-disciplinary teams at Yale’s Smilow Cancer Center in New Haven CT, and with Memorial Sloan Kettering.
For my Europe friends, I recommend Dr. Furio Pacini in Italy, and Dr. Schlumberger in France.

I hope this helps some of you out there.

Posted in Cancer, Thyroid